Mutation-related Differences in Exploratory, Spatial, and Depressive-like Behavior in Pcd and Lurcher Cerebellar Mutant Mice

Overview

Journal Front Behav Neurosci

Specialty Psychology

Date 2015 Jun 2

PMID 26029065

Citations 12

Authors

Jan Tuma

Yaroslav Kolinko

Frantisek Vozeh

Jan Cendelin

Affiliations

Soon will be listed here.

Abstract

The cerebellum is not only essential for motor coordination but is also involved in cognitive and affective processes. These functions of the cerebellum and mechanisms of their disorders in cerebellar injury are not completely understood. There is a wide spectrum of cerebellar mutant mice which are used as models of hereditary cerebellar degenerations. Nevertheless, they differ in pathogenesis of manifestation of the particular mutation and also in the strain background. The aim of this work was to compare spatial navigation, learning, and memory in pcd and Lurcher mice, two of the most frequently used cerebellar mutants. The mice were tested in the open field for exploration behavior, in the Morris water maze with visible as well as reversal hidden platform tasks and in the forced swimming test for motivation assessment. Lurcher mice showed different space exploration activity in the open field and a lower tendency to depressive-like behavior in the forced swimming test compared with pcd mice. Severe deficit of spatial navigation was shown in both cerebellar mutants. However, the overall performance of Lurcher mice was better than that of pcd mutants. Lurcher mice showed the ability of visual guidance despite difficulties with the direct swim toward a goal. In the probe trial test, Lurcher mice preferred the visible platform rather than the more recent localization of the hidden goal.

Citing Articles

Lurcher Mouse as a Model of Cerebellar Syndromes.

Roy Choudhury N, Hilber P, Cendelin J Cerebellum. 2025; 24(2):54.

PMID: 40016581 PMC: 11868327. DOI: 10.1007/s12311-025-01810-5.

Neuroprotective Effects of VEGF-B in a Murine Model of Aggressive Neuronal Loss with Childhood Onset.

Perez-Revuelta L, Perez-Boyero D, Perez-Martin E, Cabedo V, Tellez de Meneses P, Weruaga E Int J Mol Sci. 2025; 26(2).

PMID: 39859255 PMC: 11765331. DOI: 10.3390/ijms26020538.

Quantification of Solid Embryonic Cerebellar Graft Volume in a Degenerative Ataxia Model.

Purkartova Z, Krakorova K, Babuska V, Tuma J, Houdek Z, Roy Choudhury N Cerebellum. 2024; 23(5):1811-1823.

PMID: 38430389 DOI: 10.1007/s12311-024-01676-z.

Schisandrin A Alleviates Spatial Learning and Memory Impairment in Diabetic Rats by Inhibiting Inflammatory Response and Through Modulation of the PI3K/AKT Pathway.

Guo X, Lei M, Ma G, Ouyang C, Yang X, Liu C Mol Neurobiol. 2023; 61(5):2514-2529.

PMID: 37910285 DOI: 10.1007/s12035-023-03725-w.

Experimental Treatment with Edaravone in a Mouse Model of Spinocerebellar Ataxia 1.

Sucha M, Benediktova S, Tichanek F, Jedlicka J, Kapl S, Jelinkova D Int J Mol Sci. 2023; 24(13).

PMID: 37445867 PMC: 10341848. DOI: 10.3390/ijms241310689.

References

Zuo J, De Jager P, Takahashi K, Jiang W, Linden D, Heintz N . Neurodegeneration in Lurcher mice caused by mutation in delta2 glutamate receptor gene. Nature. 1997; 388(6644):769-73. DOI: 10.1038/42009. View

Triarhou L, Norton J, Ghetti B . Anterograde transsynaptic degeneration in the deep cerebellar nuclei of Purkinje cell degeneration (pcd) mutant mice. Exp Brain Res. 1987; 66(3):577-88. DOI: 10.1007/BF00270691. View

Onuki Y, van Someren E, De Zeeuw C, van der Werf Y . Hippocampal-cerebellar interaction during spatio-temporal prediction. Cereb Cortex. 2013; 25(2):313-21. DOI: 10.1093/cercor/bht221. View

Lalonde R . Immobility responses in Lurcher mutant mice. Behav Genet. 1998; 28(4):309-14. DOI: 10.1023/a:1021627631721. View

Baumann O, Borra R, Bower J, Cullen K, Habas C, Ivry R . Consensus paper: the role of the cerebellum in perceptual processes. Cerebellum. 2014; 14(2):197-220. PMC: 4346664. DOI: 10.1007/s12311-014-0627-7. View

DHooge R, De Deyn P . Applications of the Morris water maze in the study of learning and memory. Brain Res Brain Res Rev. 2001; 36(1):60-90. DOI: 10.1016/s0165-0173(01)00067-4. View

Rochefort C, Lefort J, Rondi-Reig L . The cerebellum: a new key structure in the navigation system. Front Neural Circuits. 2013; 7:35. PMC: 3595517. DOI: 10.3389/fncir.2013.00035. View

Cendelin J, Tuma J, Korelusova I, Vozeh F . The effect of genetic background on behavioral manifestation of Grid2(Lc) mutation. Behav Brain Res. 2014; 271:218-27. DOI: 10.1016/j.bbr.2014.06.023. View

Rotter A, Rath S, Evans J, Frostholm A . Modulation of GABA(A) receptor subunit mRNA levels in olivocerebellar neurons of purkinje cell degeneration and weaver mutant mice. J Neurochem. 2000; 74(5):2190-200. DOI: 10.1046/j.1471-4159.2000.0742190.x. View

10.

Marchena M, Lara J, Aijon J, Germain F, de la Villa P, Velasco A . The retina of the PCD/PCD mouse as a model of photoreceptor degeneration. A structural and functional study. Exp Eye Res. 2011; 93(5):607-17. DOI: 10.1016/j.exer.2011.07.010. View

11.

Cendelin J . From mice to men: lessons from mutant ataxic mice. Cerebellum Ataxias. 2015; 1:4. PMC: 4549131. DOI: 10.1186/2053-8871-1-4. View

12.

LaVail M, Blanks J, Mullen R . Retinal degeneration in the pcd cerebellar mutant mouse. I. Light microscopic and autoradiographic analysis. J Comp Neurol. 1982; 212(3):217-30. DOI: 10.1002/cne.902120302. View

13.

Porras-Garcia E, Sanchez-Campusano R, Martinez-Vargas D, Dominguez-Del-Toro E, Cendelin J, Vozeh F . Behavioral characteristics, associative learning capabilities, and dynamic association mapping in an animal model of cerebellar degeneration. J Neurophysiol. 2010; 104(1):346-65. DOI: 10.1152/jn.00180.2010. View

14.

Thompson R, Steinmetz J . The role of the cerebellum in classical conditioning of discrete behavioral responses. Neuroscience. 2009; 162(3):732-55. DOI: 10.1016/j.neuroscience.2009.01.041. View

15.

Ghetti B, Norton J, Triarhou L . Nerve cell atrophy and loss in the inferior olivary complex of "Purkinje cell degeneration" mutant mice. J Comp Neurol. 1987; 260(3):409-22. DOI: 10.1002/cne.902600307. View

16.

van Alphen A, Schepers T, Luo C, de Zeeuw C . Motor performance and motor learning in Lurcher mice. Ann N Y Acad Sci. 2003; 978:413-24. DOI: 10.1111/j.1749-6632.2002.tb07584.x. View

17.

OGorman S, Sidman R . Degeneration of thalamic neurons in "Purkinje cell degeneration" mutant mice. I. Distribution of neuron loss. J Comp Neurol. 1985; 234(3):277-97. DOI: 10.1002/cne.902340302. View

18.

Lalonde R, Filali M, Bensoula A, Lestienne F . Sensorimotor learning in three cerebellar mutant mice. Neurobiol Learn Mem. 1996; 65(2):113-20. DOI: 10.1006/nlme.1996.0013. View

19.

Fancellu R, Paridi D, Tomasello C, Panzeri M, Castaldo A, Genitrini S . Longitudinal study of cognitive and psychiatric functions in spinocerebellar ataxia types 1 and 2. J Neurol. 2013; 260(12):3134-43. DOI: 10.1007/s00415-013-7138-1. View

20.

Mullen R, Eicher E, Sidman R . Purkinje cell degeneration, a new neurological mutation in the mouse. Proc Natl Acad Sci U S A. 1976; 73(1):208-12. PMC: 335870. DOI: 10.1073/pnas.73.1.208. View